The overall goal of my group is to develop advanced magnetic resonance spectroscopy and imaging techniques and to apply them and other complementary methods to studying brain metabolism and neurotransmission. Magnetic resonance spectroscopy allows measurement of neurotransmission of glutamate and GABA in vivo, which play important roles in many psychiatric diseases including depression and schizophrenia. During 2006-2007, significant progress was made in the development and applications of novel spectroscopic techniques to studying metabolism, neurotransmission and specific enzyme reactions in vivo in the brain. In particular, we discovered the carbon-13 magnetization transfer effect of carbonic anhydrase and malate dehydrogenase which allows measuring their reactions in vivo. Both carbonic anhydrase and malate dehydragenase are important markers of brain disorders (J Yang, and J Shen, Relayed 13C magnetization transfer. Detection of malate dehydrogenase reaction in vivo, J Magn Reson, 184:344-349 (2007); J Yang, S Singh and J Shen, 13C saturation transfer effect of carbon dioxide-bicarbonate exchange catalyzed by carbonic anhydrase in vivo, Magn Reson Medicine, revised). We also developed an INEPT-based inverse carbon-to-proton MRS methods for detecting carbon-13 magnetization transfer using the more sensitive proton channel (S Xu, J Yang and J Shen, Inverse polarization transfer for detecting in vivo 13C magnetization transfer effect of specific enzyme reactions in 1H spectra, Magn Reson Imaging, in press). Further development of the above in vivo MRS methods for measuring enzyme reaction will be pursued using hyperpolarized carbon-13 imaging for dramatically enhanced temporal and spatial resolution. We are in the progress of investigating the effect of altered GABA on the rate of glutamate and glutamine cycling between glutamatergic neurons and astrocytes. Our results have shown that increased GABA concentration causes a reduction in the glutamate-glutamine cycling flux. We also are in the progress of writing up a paper on Monte Carlo analysis which confirmed the robustness of our two-compartment metabolic modeling of the glutamate-glutamine cycle. A method for reliable measurement of brain glutamate using proton MRS at 3 Tesla was also developed (Y Zhang, S Marenco, and J Shen, Correction of frequency drifts and phase variations induced by eddy currents in localized spectroscopy of multiple echo times, Magn Reson Med, 58:174-178 (2007)).